The Kinetic Stereocontrol in Brøsted Acid-catalyzed Pictet-Spengler Reaction and the Dynamic Epimerization Mechanism via Crystallization-induced Diastereomer Transformations

The merging of asymmetric catalysis with crystallization-induced diastereomer transformations (CIDTs) shows promise as a practical method for the synthesis of chiral molecules with one or more epimerization carbons. A successful sample is the merging of acid-catalyzed asymmetric Pictet-Spengler reaction with CIDTs for the efficient construction of chiral complex bioactive indole alkaloids like tetrahydrocarbolines. But the rule of the kinetic control is not yet fully understood. Meanwhile the structure factor on controlling the thermodynamic diastereoselectivity (beyond the solubility factor) in epimerization of 1,3-disubstituted-tetrahydro-β-carbolines via CIDTs in organic solvent/water is also unknown. For advanced understanding of the stereocontrol, the dominant non-covalent interactions would be identified based on a hydrated imine cation model. The potential of both systems as a small molecular model for future quantitative study of biologically relevant non-covalent interactions would also be discussed.